Mosquito-transmitted parasitic diseases are among the major causes of mortality and morbidity in the world. Recent dramatic increases in the incidence of mosquito-borne diseases, like malaria and dengue fever, and the wide-spread resistance of mosquitoes to insecticides underscores the need for new approaches to insect control based on mosquito- specific agents. The discovery of such mosquito-specific control agents depends on basic research on the biology of mosquitoes. Juvenile hormone (JH) is a major hormonal regulator in insects. In the female mosquito, JH signals the completion of the ecdysis to the adult stage, and initiates reproductive processes. JH titer is essentially determined by the rate at which the corpora allata (CA) synthesizes JH. The rate of CA activity is, in turn, regulated by allato-regulatory peptides that exert either allatostatic (inhibitory) or allatotropic (stimulatory) activities. During the first three years of this project we have described that allatotropin (AT) stimulates and allatostatin-C (AS-C) inhibits JH synthesis, that nutrients accumulated during the larval stages regulate CA activity, and also performed the first genomic analysis of an insect endocrine gland. Based on this work we propose that AT and AS released by the brain are essential for the activation and modulation of JH synthesis in adult female mosquitoes. The synthesis and release of these peptides is connected to nutritional signals. JH is therefore an important part of a transduction mechanism that connects changes in the nutritional status with activation of specific physiological events during reproduction. The goal of this project is to understand how peptides regulate the synthesis of JH in mosquitoes. The ultimate aim of this project is to reveal how changes in the mosquito's nutritional status are assessed and how this information is transduced to the CA. In order to test this model, in this application we propose to: 1. Investigate the mechanisms of control of JH synthesis by AT and AS-C. 2. Study the nutritional regulation of synthesis and release of AT and AS-C in the brain. Understanding the molecular basis of the physiological action of neuro-peptides will guide us in designing new and affordable agents for vector control. [unreadable] [unreadable]